Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure

This study has been completed.
Sponsor:
Information provided by:
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT00732693
First received: August 11, 2008
Last updated: NA
Last verified: August 2008
History: No changes posted
  Purpose

The aim of the study is to determine whether physiological sex steroid replacement improves parameters of skeletal, cardiovascular and reproductive health of women treated with current sex steroid replacement regimens.


Condition Intervention Phase
Premature Ovarian Failure
Drug: Ethinylestradiol / Norethisterone
Drug: Estradiol / Progesterone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparison of Standard and Physiologic Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure and the Assessment of Skeletal, Cardiovascular and Reproductive Parameters

Resource links provided by NLM:


Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • Change in 24 hour ambulatory blood pressure [ Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment ] [ Designated as safety issue: No ]
  • Bone mineral density measurements (DEXA) [ Time Frame: Baseline, 14 and 24 months ] [ Designated as safety issue: No ]
  • Uterine ultrasound scan to assess uterine volume, endometrial thickness, and uterine artery blood flow [ Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Central arterial blood pressure and arterial stiffness measured using peripheral arterial tonometry [ Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase ] [ Designated as safety issue: No ]
  • Biochemical evidence of activity on the renin-angiotensin system, including plasma renin activity, angiotensin II, aldosterone, creatinine, urea and electrolyte concentrations. [ Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase ] [ Designated as safety issue: No ]
  • Serum markers of collagen turnover and bone matrix formation [ Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase ] [ Designated as safety issue: No ]
  • Hormonal assays for gonadotrophins, FSH, LH and sex steroids estrogen and progesterone [ Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: February 2002
Study Completion Date: November 2006
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Treatment with standard sex steroid replacement regimen
Drug: Ethinylestradiol / Norethisterone
Oral ethinylestradiol 30mcg and norethisterone 1.5mg daily for weeks 1-3, followed by 7 "pill free" days
Other Name: Loestrin 30, Galen Ltd, UK
Experimental: 2
Treatment with physiologic sex steroid regimen
Drug: Estradiol / Progesterone
Transdermal estradiol 100mcg daily for week 1, then 150mcg daily for weeks 2-4; and vaginal progesterone pessaries 200mg twice daily for weeks 3-4
Other Names:
  • Estraderm TTS, Novartis Pharmaceuticals UK Ltd
  • Cyclogest, Activis UK Ltd

Detailed Description:

Premature ovarian failure, defined as the onset of the menopause before the age of 40 years, is a relatively common problem that affects 1% of women. There are a variety of aetiologies underlying premature ovarian failure including Turner syndrome and those with idiopathic onset, however with the increasing success of intensive treatment for childhood cancer, there are increasing numbers of young survivors, with a variety of late effects of treatment, including premature ovarian failure.

Evidence is required for the optimal management of young women with premature ovarian failure, either as a result of childhood cancer treatment or for other reasons. These women are currently offered combined sex steroid replacement in the convenient form of the oral contraceptive pill, or hormone replacement therapy, designed for older women after the menopause. These preparations are not designed to achieve physiological replacement of oestrogen or progesterone, either in dosage or in biochemical structure - many preparations using synthetic derivatives. These younger women who have differing metabolic and psychological requirements are looking to a future of 30 or more years of replacement. The optimal mode of SSR is not known for young women with premature ovarian failure, however there is concern that current regimens may be inadequate for optimal skeletal and cardiovascular health.

Current preliminary data demonstrates that use of physiological sex steroid replacement improves uterine parameters. Evidence is required to determine whether optimising sex steroid replacement can also significantly improve parameters of skeletal and cardiovascular health. Young women with ovarian failure face several decades of hormone replacement, so small improvements in management may make large differences to later morbidity and mortality.

The aim of the study is to determine whether physiological sex steroid replacement improves parameters of skeletal, cardiovascular and reproductive health of women treated with current sex steroid replacement regimens.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Premature Ovarian Failure

Exclusion Criteria:

  • Intercurrent illness
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00732693

Locations
United Kingdom
Royal Hospital for Sick Children
Edinburgh, United Kingdom, EH9 1LF
Royal Infirmary of Edinburgh
Edinburgh, United Kingdom, EH16 4SA
Sponsors and Collaborators
University of Edinburgh
Investigators
Principal Investigator: W Hamish B Wallace, MD NHS Lothian / University of Edinburgh
  More Information

Publications:

Responsible Party: Dr W Hamish B Wallace, Consultant/Reader in Paediatric Oncology, NHS Lothian / University of Edinburgh
ClinicalTrials.gov Identifier: NCT00732693     History of Changes
Other Study ID Numbers: CLIC/Sargent-178000-R35464
Study First Received: August 11, 2008
Last Updated: August 11, 2008
Health Authority: United Kingdom: National Health Service
United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Edinburgh:
Premature ovarian failure
Sex hormone replacement
HRT
Blood pressure
Bone mineral density
Bone metabolism
Uterine function

Additional relevant MeSH terms:
Menopause, Premature
Primary Ovarian Insufficiency
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Estradiol
Ethinyl Estradiol
Progesterone
Norethindrone
Norethindrone acetate
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Progestins
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014